COPEDOL: A two-year observational study in pretreated HIV-1-infected patients switching to a dolutegravir-based regimen.

OBJECTIVES: Dolutegravir is a second-generation integrase strand transfer inhibitor of particular interest as a rescue treatment for people living with HIV (PLWHIV) who develop resistance to multiple antiretrovirals (ART). We assessed the virological treatment response in patients switched to a dolutegravir-based regimen following failure of previous ART treatment in a real-world treatment setting. PATIENTS AND METHODS: This was a multicenter, longitudinal, observational study with retrospective patient enrolment. Patients were enrolled between February 2017 and January 2018. Patients starting dolutegravir treatment between February 2014 and September 2016 were retrospectively included. Patients were followed up for 24 months after dolutegravir initiation. During this period, treatment with dolutegravir could be discontinued at any time at the physician's discretion. Treatment failure was either defined as a viral load≥50 copies/mL at two consecutive blood samples or as clinical or biological safety issues. Overall, 459 patients were enrolled and 329 completed 24 months of treatment. The primary study outcome measures were treatment response and time to treatment response. RESULTS: 346/440 patients (78.6%) achieved a treatment response; 86 patients discontinued dolutegravir treatment (of whom 17 for failure to achieve or maintain viral suppression and 38 for tolerability issues). Acquired dolutegravir-resistance mutations were identified in five patients. CONCLUSIONS: A sustained treatment response can be obtained with a dolutegravir-based treatment regimen in PLWHIV experiencing treatment failure, even in vulnerable patients with a long history of previous ART failure, infected with multidrug-resistant HIV strains, and with multiple comorbidities.

[Therapeutic adherence in chronic obstructive pulmonary disease: A literature review]. / Revue générale sur l'adhésion aux traitements inhalés de la BPCO.

INTRODUCTION: In France, only a small number of studies have focused on therapeutic adherence in patients with chronic obstructive pulmonary disease COPD) despite its impact in terms of multimorbidity. The objective of this literature review was a better understanding of adherence as a whole, and the identification of the effects of non-adherence, in order to optimise patient management. METHODS: A search algorithm was developed to identify all publications on therapeutic adherence in COPD published between 2010 and 2017, in English and in French. The databases used were MEDLINE, ScienceDirect, BDSP, Cochrane and CAIRN. RESULTS: Of the 1551 articles initially identified, 94 were included in the review (65 observational studies, 11 interventional studies and 18 reviews or general overviews). Observational studies considered the predictive factors for adherence/non-adherence, and their consequences. Interventional studies evaluated the efficacy of interventions designed to improve adherence. CONCLUSIONS: Despite major therapeutic progress, the essential problems of COPD management remain. While the treatment armamentarium has expanded in recent years, there is still a great deal of work to be done in simplifying treatment regimens, improving the administration of these treatments and motivating patients to be compliant with them. This review also highlights the need for better physician-patient communication.

GSK256073, a selective agonist of G-protein coupled receptor 109A (GPR109A) reduces serum glucose in subjects with type 2 diabetes mellitus.

AIMS: This clinical trial assessed whether a potent, selective GPR109A agonist, GSK256073, could, through inhibition of lipolysis, acutely improve glucose homeostasis in subjects with type 2 diabetes mellitus. METHODS: Thirty-nine diabetic subjects were enrolled in the randomized, single-blind, placebo-controlled, three-period crossover trial. Each subject received placebo and two of four regimens of GSK256073 for 2 days. GSK256073 was dosed 5 mg every 12 h before breakfast and supper (BID), 10 mg every 24 h before breakfast (QD), 25 mg BID and 50 mg QD. RESULTS: The change from baseline weighted mean glucose concentration for an interval from 24 to 48 h after the initial drug dose was significantly reduced for all GSK256073 regimens, reaching a maximum of -0.87 mmol/l (-1.20, -0.52) with the 25 mg BID dose. Sustained suppression of non-esterified fatty acid (NEFA) and glycerol concentrations was observed with all GSK256073 doses throughout the 48-h dosing period. Serum insulin and C-peptide concentrations fell in concert with glucose concentrations and calculated HOMA-IR scores decreased 27-47%, consistent with insulin sensitization. No marked differences were evident between either 10 and 50 mg total daily doses or QD versus BID dosing. CONCLUSIONS: Administration of a GPR109A agonist for 2 days significantly decreased serum NEFA and glucose concentrations in diabetic subjects. Glucose improvements were associated with decreased insulin concentrations and measures of enhanced insulin sensitivity. Improved glucose control occurred with GSK256073 doses that were generally safe and not associated with events of flushing or gastrointestinal disturbances.

[Prevalence and comorbidity of psychiatric disorders in the French general population]. / Prévalence et comorbidité des troubles psychiatriques dans la population générale française: résultats de l'étude épidémiologique ESEMeD/MHEDEA 2000/ (ESEMeD).

INTRODUCTION: ESEMeD is the first international epidemiological study using a random sampling method that has allowed the prevalence of psychiatric disorders in France to be measured with precision and compared directly with that observed in other European countries. OBJECTIVES: 1) To determine the 12 month and lifetime prevalence of mood -disorders, anxiety disorders and alcohol-related disorders. 2) To estimate the comorbidity between these disorders. 3) To evaluate potential demographic risk factors for these disorders. METHODS: This was a transversal survey carried out between 2001 and 2003 of non-institutionalised subjects aged 18 or over in the general population of Germany (n = 3,555), Belgium (n = 2,419), Spain (n = 5,473), France (n = 2,894), the Netherlands (n = 2,372) and Italy (n = 4,712). In France, the sampling source was a randomly generated list of telephone numbers. Subjects were interviewed at home by professional interviewers. The WMH-CIDI questionnaire was used. RESULTS: The participation rate was 46% for France and 61% for all six countries combined. The 12 month and lifetime prevalence rates observed were respectively 6.0% and 21,4% for major depressive episodes, 1.6% and 7.9% for dysthymia, 2.1% and 6.0% for the generalised -anxiety disorders, 1.2% and 3.0% for panic disorders, 0.6% and 1.8% for agoraphobia, 2.2% and 3.9% for post-traumatic stress disorder, 1.7% and 4.7% for social phobia, 4.7% and 11,6% for specific phobia, 0.5% and 4.1% for alcohol abuse and 0.3% and 1.6% for alcohol dependence. Mood disorders and anxiety disorders were significantly more frequent in women, whilst alcohol-related disorders were more frequent in men. The prevalence of all three types of disorder was lower in elderly subjects and in those living in a rural environment. Mood disorders and alcohol-related disorders were more frequent in individuals living alone and mood disorders more frequent in those without paid employment. 38% of subjects with mood disorder also presented an anxiety disorder or an alcohol-related disorder. The comorbidity of mood and anxiety disorders was more frequent in women, younger subjects and those living alone. The comorbidity rate in subjects with anxiety disorders was 26% and did not differ between genders. For alcohol-related disorders, there was a striking difference in comorbidity rate between men and women: 26% in the former and 67% in the latter. CONCLUSION: This study underlines the high prevalence of mood disorders, anxiety disorders and alcohol-related disorders in France and demonstrates a high degree of comorbidity between them. For this reason, it is important to evaluate and take into account potential comorbidity in the management of individuals with psychiatric disorders.

[Psychotropic drug use and mental psychiatric disorders in France; results of the general population ESEMeD/MHEDEA 2000 epidemiological study]. / Usage des psychotropes et troubles psychiatriques en France: résultats de l'étude épidémiologique ESEMeD/MHEDEA 2000/ (ESEMeD) en population générale.

INTRODUCTION: The use of psychotropic drugs is high in France and has increased over the last two decades. To date, no national study evaluating psychotropic drug use in the context of the diagnosis of psychiatric disorders has been performed. Such data has now been generated in the ESEMeD/MHEDEA 2000 study, which has allowed comparison of the situation in France with that in five other European countries (Germany, Belgium, Spain, the Netherlands and Italy). OBJECTIVES: 1) To describe the declared use of psychotropic drugs (globally and by therapeutic class) in order to evaluate annual prevalence, treatment duration and demographic factors associated with use. 2) To estimate the proportion of subjects with an anxiety disorder, mood disorder or alcohol-related disorder (abuse or dependence) that have been appropriately treated with an antidepressant or anxiolytic drug. 3) to evaluate the proportion of psychotropic drug users who fulfil diagnostic criteria for these three classes of psychiatric disorder. METHODS: This was a transversal survey carried out between 2001 and 2003 of non-institutionalised subjects aged 18 or over in the general population of Germany (n = 3,555), Belgium (n = 2,419), Spain (n = 5,473), France (n = 2,894), the Netherlands (n = 2,372) and Italy (n = 4,712). In France, the sampling source used was a randomly generated list of telephone numbers. Subjects were interviewed at home by professional interviewers. The WMH-CIDI questionnaire was used. RESULTS: In France, 21% of subjects interviewed (n = 580) had taken at least one psychotropic drug during the year. For 19%, this was an anxiolytic or hypnotic (AX-HY), for 6.0% an antidepressant (AD), for 0.8% an antipsychotic (AP) and for 0.4% a mood regulating drug (TY). The distribution of users of AX-HY according to treatment duration was the following: 44% (1 to 15 days), 13% (16 to 30 days), 14% (1 to 3 months), 6.7% (3 to 6 months) and 23% (> 6 months). For users of ADs, the distribution was: 21% (1 to 15 days), 7.8% (16 to 30 days), 18% (1 to 3 months), 12% (3 to 6 months) and 42% (> 6 months). For subjects fulfilling diagnostic criteria for a mood disorder in the previous year or over their lifetime, 43% and 29% respectively had taken an AX-HY in the last twelve months and 29% and 16% an AD. For those who fulfilled diagnostic criteria for an anxiety disorder in the previous year or over their lifetime, the use of an AX-HY, in the last twelve months, concerned 43% and 30% of subjects respectively, whilst that of AD concerned 16% and 14%. For previous year or lifetime alcohol-related disorders, AX-HY use, in the last twelve months, concerned 63% and 22% of subjects respectively and use of ADs 9.3% and 7.2%. Amongst users of AX-HY in the last twelve months, a previous year or lifetime diagnosis of mood disorders was made for 16% and 39% of subjects respectively. Amongst users of ADs, the respective prevalence was 31% and 64%. A twelve-month and lifetime diagnosis of anxiety disorders was identified in 22% and 37% of users of AX-HY and among 27% and 50% of users of AD respectively. A twelve-month and lifetime diagnosis of alcohol-related disorders was found in 2.5% and 6.6% of users of AX-HY and among 1.1% and 7.8% of users of AD respectively. 68% of users of AX-HY had fulfilled none of these diagnostic criteria in the previous 12 months and 46% had never fulfilled them in their lifetime. With respect to AD users, the proportion who did not meet these diagnostic criteria in the previous 12 months was 56%, compared to 20% over their lifetime. Comparison of the French data from the study with those of the entire European sample showed that the annual prevalence of AX-HY and AD use was higher in France with mean treatment durations that were shorter. For antipsychotics and mood regulators, no clear differences were observed between France and the six countries of the study taken together. DISCUSSION: Over the last two decades, use of AX-HY seems to have decreased in France, even though it remains higher than that observed in the other European countries participating in this study. This high use can be explained in part by the observation that, in around half the cases, it corresponds to occasional use. In contrast, the use of antidepressants has increased. In subjects with recent mood disorders or anxiety disorders, the use of AX-HY remains higher than that of antidepressants. Finally among users of AX-HY, only half of them had presented a mood disorder, anxiety disorder or alcohol use disorder during their lifetime, whereas this proportion rose to 80% for users of antidepressants.